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Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings
BACKGROUND: Recent scientific advances in cancer research have led to the development of immunomodulatory and molecularly targeted drugs with better safety profiles than chemotherapeutics, which makes it possible to include healthy volunteers (HVs) in clinical trials. In this study, we aimed to iden...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688384/ https://www.ncbi.nlm.nih.gov/pubmed/34379306 http://dx.doi.org/10.1007/s43441-021-00330-8 |
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author | Omes-Smit, Grace Garsen, Marjolein Zwiers, Alex |
author_facet | Omes-Smit, Grace Garsen, Marjolein Zwiers, Alex |
author_sort | Omes-Smit, Grace |
collection | PubMed |
description | BACKGROUND: Recent scientific advances in cancer research have led to the development of immunomodulatory and molecularly targeted drugs with better safety profiles than chemotherapeutics, which makes it possible to include healthy volunteers (HVs) in clinical trials. In this study, we aimed to identify the number of marketing authorization applications (MAAs) that enrolled HVs in a clinical trial and to identify the number of anticancer drugs that were given to HVs despite a positive genotoxic finding. In addition, we evaluated the dose of anticancer drugs administered to HVs and the justification for proceeding with HV studies despite a positive genotoxic finding. METHODS: Publicly available information from the European Medicines Agency (EMA) website was used for this study. Anticancer drugs were identified using the human medicines highlights published by EMA between January 2010 and December 2019. EPARs were used to collect general information of the anticancer drugs, details on genotoxicity studies, and the enrollment of HVs in clinical trials. RESULTS: We identified 71 MAAs for small molecule anticancer drugs with a positive or negative CHMP opinion in the EU. Forty-eight anticancer drugs were studied in HVs, of which 12 anticancer drugs were administered to HVs despite positive genotoxic findings in the standard battery. Systematic and extensive genetic toxicology screening demonstrated the absence of genotoxic risks to the cell system. CONCLUSION: We showed that despite a positive genotoxic finding, comprehensive genetic toxicology testing demonstrated the absence of risks to the cell system at the human exposure dose. Therefore, these anticancer drugs posed no harm to HVs. |
format | Online Article Text |
id | pubmed-8688384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-86883842021-12-22 Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings Omes-Smit, Grace Garsen, Marjolein Zwiers, Alex Ther Innov Regul Sci Original Research BACKGROUND: Recent scientific advances in cancer research have led to the development of immunomodulatory and molecularly targeted drugs with better safety profiles than chemotherapeutics, which makes it possible to include healthy volunteers (HVs) in clinical trials. In this study, we aimed to identify the number of marketing authorization applications (MAAs) that enrolled HVs in a clinical trial and to identify the number of anticancer drugs that were given to HVs despite a positive genotoxic finding. In addition, we evaluated the dose of anticancer drugs administered to HVs and the justification for proceeding with HV studies despite a positive genotoxic finding. METHODS: Publicly available information from the European Medicines Agency (EMA) website was used for this study. Anticancer drugs were identified using the human medicines highlights published by EMA between January 2010 and December 2019. EPARs were used to collect general information of the anticancer drugs, details on genotoxicity studies, and the enrollment of HVs in clinical trials. RESULTS: We identified 71 MAAs for small molecule anticancer drugs with a positive or negative CHMP opinion in the EU. Forty-eight anticancer drugs were studied in HVs, of which 12 anticancer drugs were administered to HVs despite positive genotoxic findings in the standard battery. Systematic and extensive genetic toxicology screening demonstrated the absence of genotoxic risks to the cell system. CONCLUSION: We showed that despite a positive genotoxic finding, comprehensive genetic toxicology testing demonstrated the absence of risks to the cell system at the human exposure dose. Therefore, these anticancer drugs posed no harm to HVs. Springer International Publishing 2021-08-11 2022 /pmc/articles/PMC8688384/ /pubmed/34379306 http://dx.doi.org/10.1007/s43441-021-00330-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Research Omes-Smit, Grace Garsen, Marjolein Zwiers, Alex Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings |
title | Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings |
title_full | Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings |
title_fullStr | Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings |
title_full_unstemmed | Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings |
title_short | Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings |
title_sort | healthy volunteer studies in the development of anticancer drugs with genotoxic findings |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688384/ https://www.ncbi.nlm.nih.gov/pubmed/34379306 http://dx.doi.org/10.1007/s43441-021-00330-8 |
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